A problem with the administration of many pharmaceutical medicaments and diagnostic compounds has been the need to retain sufficient quantities of these compounds in contact with the target tissues and systems for a sufficient period of time to accomplish the therapeutic or diagnostic purpose. This problem is particularly acute in connection with compounds administered to the eye. In the ocular environment, tear turnover and drainage through the lacrimal system quickly remove a major portion of any compound administered to the eye so that only a small fraction of the original dosage remains in the eye for an extended period of time. As a result, the repeated administration of relatively large dosages is required to compensate for this loss and to ensure that an effective concentration of the desired pharmaceutical agent remains in contact with the eye. Similar problems are also encountered in connection with the nasal mucosa, oral cavity and similar physiologic environments.
An alternative approach to ophthalmic drug retention in the eye has been the use of viscous ointments and gels designed to slow down the rapid loss of pharmaceutical compounds. These semi-solid drug containing compounds are applied directly to the conjunctiva of the eye and remain in the cul de sac until physically or mechanically removed. Though reasonably effective at retaining adequate drug dosages in contact with the surface of the eye, a major disadvantage associated with ointments and gels is the difficulty of delivering a controlled dosage with such widely variable systems. To date, it has not been possible to deliver preformed gels from multiple dose containers in a ready and convenient fashion. Moreover, previously known drug containing ointments and gels may form barriers to sight as well as forming aesthetically unpleasant crusting along the edges of the eyelids. This and possible blockage of the lacrimal duct may lead to decreased patient acceptability and utilization of such systems.
Another approach to the solution of these problems has been the utilization of drug containing ocular inserts. Typically, these devices are formed of microporous solid polymers incorporating a reservoir of the drug or diagnostic agent required. Shaped as a small disc, barrel or strip, these devices are inserted into the cul de sac of the eye where they remain for periods of several days or weeks while the pharmaceutical compounds contained therein continuously diffuse into the lacrimal fluids. A significant disadvantage associated with such solid insert devices is that many patients, especially the elderly, have a difficult time inserting or removing a solid object from the cul de sac of the eye. As a result, it is often necessary for medical personnel to position such devices as well as to remove them at the end of their useful life. What is more, currently available ocular inserts often fall out of position from the eye. Additionally, these devices may be uncomfortable when placed in the eye.
Another alternative approach to the solution of these problems has been the utilization of drug delivery compounds which are liquid at room temperature, but which form semi-solid compounds when warmed to body temperatures. Similarly, compositions which transform from liquids to semi-solids in response to changes in pH have also been proposed. Though effective at their intended purposes, such compounds may suffer from many of the drawbacks associated with ointments and gels and still may require repeated administration throughout the day.
Alternatively, bioerodible microparticulate suspensions have also been utilized for the delivery of ophthalmic drugs. For example, U.S. Pat. No. 4,001,388 discloses an orthoester homopolymer drug containing microparticulate suspended in a liquid carrier such as physiological saline, silicone oil, mineral oil and the like. Similarly, U.S. Pat. No. 4,865,846 discloses a drug delivery system formed of a liquid and ointment carrier containing an ophthalmic drug and a bioerodible particulate carrier incorporating additional drugs. The bioerodible feature is designed to prevent the buildup of particulate material in the eye, as well as to provide controlled drug release. However, in practice, significant loss through the lacrimal drainage system decreases the effectiveness of such delivery systems.
Accordingly, it is a principal object of the present invention to provide a sustained release drug delivery vehicle for use in treating or diagnosing ophthalmic conditions as well as for use in physiological environments similar to the ocular milieu.
It is an additional object of the present invention to provide an erodible ocular drug delivery vehicle which can be installed in the cul de sac of the eye without need for professional medical assistance and which obviates the need for subsequent removal of the vehicle by the patient or medical personnel.
It is a further object of the present invention to provide an ophthalmic drug delivery vehicle which is self-lubricating for patient comfort, yet which exhibits muco-adhesive properties for retention on the conjunctival mucosa.
It is a further additional object of the present invention to provide an ophthalmic drug delivery vehicle that can be conveniently administered in controlled dosages at daily or weekly intervals, or more often if desired.